FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2334910644> ?p ?o ?g. }

• W2334910644 abstract "You have accessJournal of UrologyBladder Cancer: Basic Research II1 Apr 2012894 4-METHYLUMBELIFERONE A POTENTIAL ANTI-METASTATIC ORAL AGENT FOR BLADDER CANCER Michael Garcia-Roig, Travis Yates, Anaid Benitez, and Vinita Lokeshwar Michael Garcia-RoigMichael Garcia-Roig Miami, FL More articles by this author , Travis YatesTravis Yates Miami, FL More articles by this author , Anaid BenitezAnaid Benitez Miami, FL More articles by this author , and Vinita LokeshwarVinita Lokeshwar Miami, FL More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.989AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Elevated Hyaluronic Acid (HA) levels are a molecular determinant of bladder cancer (BCa) metastasis. Furthermore, HA, HYAL-1 hyaluronidase and HA-synthesizing enzymes are potential markers for BCa diagnosis and predicting prognosis. 4-Methylumbelliferone (4-MU) is an orally bioavailable dietary supplement that inhibits HA synthesis. Epithelial mesenchymal transition (EMT) is the hallmark of invasion and metastasis, in which cancer cells acquire an invasive phenotype. Since HA promotes tumor metastasis, we evaluated the antitumor effects of 4-MU in vitro and in vivo and examined whether 4-MU can reverse the EMT by inhibiting HA synthesis. METHODS Quantitative PCR was used to measure mRNA expression of EMT genes (β;-catenin, Twist, and Snail) in 66 bladder tissue specimens (27 normal; 39 tumor); follow-up: 26±4.3 months; median 20 months. The effect of 4-MU (0.2 – 0.6 mM) on cell proliferation, apoptosis, intracellular signaling, and the expression of HA receptors and EMT genes were examined in BCa cell lines, 253J-Lung and HT1376. Effect of 4-MU on tumor growth was analyzed in subcutaneous xenografts. RESULTS Among the EMT genes, both Snail and Twist were differentially expressed in BCa tissues when compared to normal bladder (P<0.001). Furthermore, Twist expression significantly correlated with metastasis (+: 0.25+0.15, - : 0.12+0.14; P=0.028). β-catenin expression negatively correlated with survival (chi square=4.3, p=0.038). 4-MU inhibited proliferation and induced apoptosis in the BCa cells. Following a 48 h exposure at the IC50 for HA synthesis (0.4 mM), 4-MU inhibited proliferation by 61% and increased apoptosis by 73%. 4-MU induced caspase-8, -9 and -3 activation and up-regulation of Fas and FADD. 4-MU downregulated the expression of HA-receptors - CD44, RHAMM, EMT promoters - β;-catenin, Snail and Twist by 4-10-fold, but increased the expression of E-cadherin by 2-fold, suggesting EMT-reversal. In xenograft studies, 4-MU significantly decreased tumor growth (> 3-fold) when treatment was started either on the day of tumor cell injection or after tumors became palpable. No weight loss or serum or organ toxicity was observed in treated mice. Tumors showed reduced microvessel density (∼3-fold) and HA expression but increased TURNEL positive cells. CONCLUSIONS This is the first study that shows inhibition of HA synthesis by an orally bioavailable, non-toxic supplement that potentially reverses EMT and has potent anti-tumor activity. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e364 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Michael Garcia-Roig Miami, FL More articles by this author Travis Yates Miami, FL More articles by this author Anaid Benitez Miami, FL More articles by this author Vinita Lokeshwar Miami, FL More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ..." @default.
• W2334910644 created "2016-06-24" @default.
• W2334910644 creator A5036828039 @default.
• W2334910644 creator A5054159165 @default.
• W2334910644 creator A5070622996 @default.
• W2334910644 creator A5085602878 @default.
• W2334910644 date "2012-04-01" @default.
• W2334910644 modified "2023-09-25" @default.
• W2334910644 title "894 4-METHYLUMBELIFERONE A POTENTIAL ANTI-METASTATIC ORAL AGENT FOR BLADDER CANCER" @default.
• W2334910644 doi "https://doi.org/10.1016/j.juro.2012.02.989" @default.
• W2334910644 hasPublicationYear "2012" @default.
• W2334910644 type Work @default.
• W2334910644 sameAs 2334910644 @default.
• W2334910644 citedByCount "0" @default.
• W2334910644 crossrefType "journal-article" @default.
• W2334910644 hasAuthorship W2334910644A5036828039 @default.
• W2334910644 hasAuthorship W2334910644A5054159165 @default.
• W2334910644 hasAuthorship W2334910644A5070622996 @default.
• W2334910644 hasAuthorship W2334910644A5085602878 @default.
• W2334910644 hasConcept C121608353 @default.
• W2334910644 hasConcept C126322002 @default.
• W2334910644 hasConcept C142724271 @default.
• W2334910644 hasConcept C150903083 @default.
• W2334910644 hasConcept C207001950 @default.
• W2334910644 hasConcept C26291073 @default.
• W2334910644 hasConcept C2779013556 @default.
• W2334910644 hasConcept C2780352672 @default.
• W2334910644 hasConcept C502942594 @default.
• W2334910644 hasConcept C71924100 @default.
• W2334910644 hasConcept C86803240 @default.
• W2334910644 hasConcept C96232424 @default.
• W2334910644 hasConceptScore W2334910644C121608353 @default.
• W2334910644 hasConceptScore W2334910644C126322002 @default.
• W2334910644 hasConceptScore W2334910644C142724271 @default.
• W2334910644 hasConceptScore W2334910644C150903083 @default.
• W2334910644 hasConceptScore W2334910644C207001950 @default.
• W2334910644 hasConceptScore W2334910644C26291073 @default.
• W2334910644 hasConceptScore W2334910644C2779013556 @default.
• W2334910644 hasConceptScore W2334910644C2780352672 @default.
• W2334910644 hasConceptScore W2334910644C502942594 @default.
• W2334910644 hasConceptScore W2334910644C71924100 @default.
• W2334910644 hasConceptScore W2334910644C86803240 @default.
• W2334910644 hasConceptScore W2334910644C96232424 @default.
• W2334910644 hasIssue "4S" @default.
• W2334910644 hasLocation W23349106441 @default.
• W2334910644 hasOpenAccess W2334910644 @default.
• W2334910644 hasPrimaryLocation W23349106441 @default.
• W2334910644 hasRelatedWork W1499339123 @default.
• W2334910644 hasRelatedWork W1972952460 @default.
• W2334910644 hasRelatedWork W2154708791 @default.
• W2334910644 hasRelatedWork W2568845480 @default.
• W2334910644 hasRelatedWork W2946712055 @default.
• W2334910644 hasRelatedWork W3173207637 @default.
• W2334910644 hasRelatedWork W3202872612 @default.
• W2334910644 hasRelatedWork W4213439341 @default.
• W2334910644 hasRelatedWork W4283771460 @default.
• W2334910644 hasRelatedWork W4304116770 @default.
• W2334910644 hasVolume "187" @default.
• W2334910644 isParatext "false" @default.
• W2334910644 isRetracted "false" @default.
• W2334910644 magId "2334910644" @default.
• W2334910644 workType "article" @default.